The present invention relates to the monitoring of a material, such as (but not limited to) a blood component, that can serve, intentionally or unintentionally, as a growth medium for the growth of microorganisms such as bacteria, and that is contained within a sealed container, and, more particularly, to such monitoring in real time and in a non-invasive manner, i.e., without opening the container and withdrawing a portion of the material e.g. for incubation in another growth medium in a separate container. Such materials are called “biological materials” herein.
The primary intended application of the invention is to detecting bacterial contamination of a biological material such as platelets; but the scope of the invention is wider than this primary intended application and is defined by the appended claims.
Platelets are a component of blood that is involved in blood clotting. Blood components such as red blood cells, white blood cells, plasma and platelets, commonly are used for transfusions. Platelet transfusions often are given to patients undergoing procedures such as chemotherapy for leukemia, bone marrow transplants, radiation treatment, organ transplants, and surgeries such as cardiopulmonary bypass, and as therapy for medical conditions including multiple myeloma, aplastic anemia, AIDS, hypersplenism, idiopathic thrombocytopenic purpura and sepsis.
Isolation of platelets for transfusion is effected by one of two methods: isolation from collected units of whole blood units or collection by apheresis.
Allogenic blood for transfusion is a potential source of infection by a variety of known and unknown transmissible agents. Over the last three decades, the risk of transfusion-related transmission of viral diseases such as human immunodeficiency virus (HIV) I/II, hepatitis C virus (HCV), hepatitis B virus (HBV) and human T-lymphotropic virus (HTLV) I/II has decreased dramatically. With blood products now being routinely screened by ultrasensitive techniques to minimize the risk of transmitting viruses to recipients, the known risk of transmission of bacteria has emerged as the greatest residual threat of transfusion-transmitted disease. Bacterial contamination has proved more difficult to address than viral contamination, and remains the most prevalent transfusion-associated infectious risk. This is especially true for platelets, which are stored at room temperature (22° C.) for up to five days (rather than the previous practice of storage for up to seven days), in bags that are permeable to oxygen and carbon dioxide, and under sufficient constant agitation to provide adequate oxygenation, to prevent platelet aggregation and to maintain optimal platelet viability and functional properties. Storage at room temperature provides an environment where any bacteria that are introduced to the blood component during the collection process may proliferate and subsequently cause bacteremia in the patient. The risk of bacterial contamination in platelets is estimated to be one in 1500, which is one to two orders of magnitude greater than the combined risk of viral infections (S. Ribault et al., Rapid screening method for detection of bacteria in platelet concentrates, Clinical Microbiology vol. 2 (2004) pp. 1903-1908).
Sussman et al., U.S. Pat. No. 5,155,019, test for the presence of microorganisms in a possibly contaminated substance by transferring some of the substance to a sterile vial that is impermeable to carbon dioxide and that includes a growth medium for the microorganisms, sealing the vial, incubating the vial and using infrared spectroscopy to monitor the concentration of carbon dioxide in the head space above the growth medium in the vial. The vial is positioned between a source of a beam of infrared radiation and a detector of the beam so that the beam traverses the head space.
Berndt, U.S. Pat. No. 5,482,842 teaches a similar method, but uses two sources and two detectors. Bachur et al. EP 1 724 335 A1, teach a similar method that uses one or more tunable lasers as the infrared source(s). Hoberman, U.S. Pat. No. 4,889,992, teaches a vial that is adapted for use in such methods: the vial includes a passive mechanism for keeping liquid and foam from the growth medium out of the path of the infrared beam.
U.S. Pat. No. 5,155,019, U.S. Pat. No. 5,482,842, EP 1 724 335 A1 and U.S. Pat. No. 4,889,992 all are incorporated by reference for all purposes as if fully set forth herein. The methods taught therein are not suitable for monitoring bacterial contamination of platelets because those methods would require transfer of some platelets from a platelet bag to a vial that includes a growth medium, followed by incubation of the vial. Aside from increasing the risk of inadvertent contamination of the remaining platelets, these methods require incubation time and so may be inconsistent with the relatively short shelf life of platelets.
It would be highly advantageous to have an in-situ, real-time, non-invasive method of monitoring platelet bags for bacterial contamination.